We will construct a LC Microdispenser system for rapid liquid chromatography and high throughput loading of digested protein samples onto MALDI-TOF MS targets. This system will incorporate automated preparation of the reversed phase column, including automatic sample loading and integration into the microdispensing device. The capacity of the multi-fluid print head will be increased to 20 different fluids to increase throughput for multiple samples and/or to allow for different chromatography treatments. This system will provide for the maximum conservation of sample volume combined with the rapid LC separation of peptides, resulting in improved MALDI-TOF MS analysis through a reduction in ion suppression. The function and sensitivity of the LC Microdispensor system will be verified by the detection and peptide mass fingerprinting of low abundance proteins in Saccharomyces cerevisiae. Commercialization efforts will be conducted in parallel with the research efforts, in collaboration with our commercialization partners: Proteome Systems, Ltd., Shimadzu Biotech, and Millipore Corporation. Commercial Applications: High throughput instrumentation that improves the sensitivity and dynamic range during MALDI-TOF MS and results in the peptide mass fingerprinting of low abundance proteins is highly desired in the rapidly developing field of proteomics. Details regarding protein expression and post-translational modifications can reveal processes within a biological system useful for drug discovery and the diagnosis and treatment of disease and cancer.